Immunization of BALB/c or CB6F1 mice to heterologous erythrocytes induces multiple regulatory T cells that can initially be segregated by their ability to selectively modulate either clone growth or secretory differentiation of the anti-TNP IgA-secreting BALB/c myeloma MOPC-315 in the presence of TNP-conjugated heterologous erythrocytes. The target for both the proliferation and differentiation helper and suppressor T cells appears to be the small, nonsecretory lymphocytoid MOPC-315 tumor stem cells. The purpose of the experiments is to produce monoclonal lines of each helper and suppressor T cell induced by sheep erythrocyte immunization of CB6F1 mice and to characterize each monoclonal regulatory cell as to its triggering requirements for proliferation and regulatory factor secretion, specificity of cell surface receptors, cell cycle alterations in receptor expression, and regulatory factor secretion. The ability of the SRBC-immune regulatory T cells that recognize IgA315 to influence normal anti-SRBC antibody responses and idiotype 315-positive anti-TNP antibody responses will also be investigated. The soluble regulatory factors will be serologically and biochemically characterized. Of special interest will be the determination of whether the IgA315-recognizing, SRBC-immune regulatory T cells secrete two factors (one specific for SRBC and one for IgA315 idiotopes) or whether they act through nonspecific factors. An investigation of factor-mediated alterations in the 315 cell cycle will also be done. The ability of SRBC-specific factors secreted by the cloned secretory differentiation TH cells and the proliferation TS cells to act therapeutically against established and developing MOPC-315 and its light chain variant (SS5A) when focused through TNP-SRBC, anti-IgA-SRBC, or anti-lambda2-SRBC will be investigated. We will also try to delineate the cellular mechanisms by which any tumor growth inhibition (or cure) is mediated. These experiments will yield much information about structure-function relationships of various regulatory factors that are functionally distinct but act on the same target cell. Information about the efficacy of using such monoclonal regulatory factors to control malignant B-cell tumors will also be obtained. (LB)